NO743213L - - Google Patents

Description

Application of the pregnancy

specific Ø^-glycoprotein and its

antibody to contraception.

The object of the invention is the use of the pregnancy-specific fi^-glycoprotein (SP^) and its antibodies to con-? prevention of sepsis and the provision of abortion.

It has already been attempted using antisera

against extracts of animal plants in rabbits to prevent conception and in monkeys and mice to cause abortion. Attempts have also already been made to reduce the degree of obesity in rats by active immunization with human placental lactogen. All these experiments have not progressed beyond an initial stage and have not found special application in medicine.

It has now been found that the pregnancy-specific glycoprotein, which can be extracted from placenta or serum and an antiserum can be used to prevent conception and to induce abortion in primates, e.g. in humans and in monkeys.

SP-^ is a known compound such as e.g. occurs in the blood of pregnant women* It belongs to the pregnancy-specific proteins and probably forms in the syncytiotrophoblast of the placenta. It can e.g. is extracted according to the method according to application no. P 21 57 610.3 from placenta or serum or urine of pregnant women. So far, SP^ has not yet been used to prevent conception or to provide an abortion.

The use of S?^ to prevent pregnancy can take place directly by active immunization of the recipient. To this end, an effective amount of SP^ is administered to the recipient by injection. The administration conveniently takes place in several, time-ordered single injections, preferably intravenously. The total dose, which is to be distributed over the individual injections, has to follow the recipient's weight and amounts to a few milligrams per kg or less, preferably approx. 0.2 to 10 mg/kg. In addition, the single injection results in a dose from a fraction of a milligram to a milligram per kg body weight of the recipient. The administration conveniently takes place in the form of a solution of SP^ in a physiologically tolerable liquid such as isotonic saline solution.

In addition to active immunization, kari SP is also used in the form of an antiserum to prevent pregnancy. In addition, it is mined on

antisera from suitable experimental animals, e.g. from horses, cattle, goats or rabbits. From such antisera, the antibodies can then be isolated according to known methods, for example by salting out (e.g. precipitation with ammonium sulfate) or by chromatographic methods (e.g. using DEAE cellulose, preferably in the form of a column). The antibodies thus formed can, if desired, be lyophilized and are stable for several years in this form.

A particular advantage of the use of SP^ is its immunological mode of action. In this way, it is superior to any physical or chemical precaution. Side effects, which have become known for the methods used so far, were not observed.

The invention shall be explained in more detail with the help of some examples, without the subject matter of the invention being limited to these examples.

Example 1.

Extraction of antisera and purification of antibodies.

40 rabbits are immunized with the pregnancy-specific {J^-glycoprotein. From the animals' serum, the antibodies are isolated by precipitation with (NHjjJjSOjjOOJf w/v) and by chromatography using DEAE- _

cellulose and Q.04 molar phosphate buffer pH 7.0. The antibodies thus travel unimpeded through the column, the other serum proteins remain

bound on the DEAE cellulose. The eluate with the antibodies is initially concentrated to 5% egg white, mixed with 2x25% glycine, sterile filtered, filled in portions of 5 ml and lyophilized. Each filling contains 250 mg of egg white.

Example 2.

Termination ay pregnancy.

On sexually mature female monkeys of the genus Cynomolgus, the cycle for the individual animals is determined by daily vaginal smears. At the time of ovulation determined from this, the two days of hahdyr are brought together. The detection of sperm in the vagina serves as a control

of fertilization. 17, 18 and 19 days after fertilization, a serum sample is taken and examined in a mouse sample. The samples of most animals were positive and showed a pregnancy. Between the 30th and 40th day of pregnancy, eight of the pregnant animals on three consecutive days each time receive 250 mg of the antibody preparation from the rabbit serum against the pregnancy-specific 8^-glycoprotein (produced according to example 1) dissolved in 5 ml intravenously administered. Within a<y>few days after

The last injection resulted in abortion in all cases. Two pregnant ferrets that were treated analogously received a correspondingly prepared antibody preparation which was made from normal rabbit serum and did not contain any antibody against the human pregnancy-specific ØjTglycoprotein. They carried out the pregnancy normally and gave birth to healthy children.

Example 3.

Contraception by means of antiserum. « 5 sexually mature female monkeys were given two days before the expected one

ovulation each time 250 mg of the antibody preparation from rabbit serum

against the pregnancy-specific Ø^-glycoprotein (produced according to

example 1) injected intravenously. At the time of ovulation, they are mated with males. Detection of sperm in the vagina serves

(fertilization control. 17, 18 and 19 days after fertilization, serum samples are taken and examination in a mouse sample. For all animals, the samples are

Claims (4)

negative, the monkeys were not pregnant. The serum of untreated control animals was positive in the muBé test and they gave birth to live children. Example 4. Obstruction of conception by active immunization. Two sexually mature female monkeys are actively immunized with pregnancy-specific f^-glycoprotein, whereby 4 mg of the pregnancy-specific f^-glycoprotein, dissolved in physiological sodium chloride solution, is administered intravenously to each monkey in several portions over a period of a few days. The immunization extends over a period of 5-6 weeks. Antibodies against the pregnancy-specific 8^-glycoprotein are then examined. Both sera were positive. 2 days before the calculated ovulation and further every two days before the following calculated ovulation dates, immunized monkeys are brought together each time for 5 days with male monkeys. Once 17, 18 and 19 days after mating, a serum sample was examined in a mouse sample. All samples were negative. Consequently, a pregnancy had not occurred. The experiments that extended over a longer period of time to fertilize female monkeys that had been pre-treated with pregnancy-specific 3^-glycoprotein were thus uterine results. Use of the pregnancy-specific J^-glycoprotein and its antibodies to prevent conception and to induce abortion in primates.